Basic esters of substituted beta-hydroxypropionic acids and preparation thereof



limited States PatentO 2 996 53s BASIC ESTERS F suBsTITUTEn p-HYDROXY- 5%0PIONIC ACIDS AND PREPARATION Frederick F. Blicke, Ann Arbor, Mich., assign'or to Regents of The University of Michigan, Ann Arbor, Mich., a corporation of Michigan No Drawing. Filed June 10, 1954, Ser. No. 435,921

26 Claims. (Cl. 260-468) This invention relates to basic esters of substituted p-hydroxypropionic acids having the formula wherein R is a member of the class consisting of the cyclohexyl group and lower-alkyl-substituted cyclohexyl groups, R is a member of the class consisting of hydrogen, lower-alkyl, cycloalkyl and lower-alkyl-substituted cyoloalkyl groups, R is a member of the group consisting of cycloalkyl, lower-alkyl-substituted cycloalkyl and iower-alkyl groups which may be joined with R to form a cycloalkyl or lower-alkyl-substituted cycloa-lkyl group, Y is a lower-alkylene bridge having the free valances on diiferent carbonatoms, and N B is a member of the class consisting. of di-lower-alkylamino, .polymethylenimino radicals having 5- to S-membered rings and morpholino radicals.

The invention also relates to a process tor the preparation of these new compounds, and to intermediates in their preparatioiii These new compounds are useful in the form of their water-so1uble, non-toxic salts as antispasmodic agents.

In the above general formula, R represents a cyclohexyl or a lower-alkylated cyclohexyl group. In the loweralkylated cycloheX-yl' groups the alkyl groups can contain from one to about [four carbon atoms and therecan be from one to three such groups attached to the cyclohexyl ring. Accordingly R includes such groups as'cyclohe'xyl,

4-methylcyclohexyl, 4-ethylcyclohexyl, 2,4-dimethylcyclohexyl, 2,4,G-trimethylcyclohexyl, 4-butylcyclohexyl, andthe like- 'In the above general formula, R represents a'hydro gen atom or a lower-alkyl, cycloalkyl, or lower-alkylsubstituted cy-cloalkyl group. The lower-alkyl groupsican' contain from one to about eight carbon atoms andmay be straight or'branched, and the cycloalkyl groups include alicyolic rings in which there are from five toeight carbon atoms in the ring; Accordingly R includes such groups as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary-butyl, amyl, isoamyl, hexyl, heptyl, octyl, cyclopentyl, Z-methylcyclopentyl, cyclohexyl, 4-methylcyclohexyl, cycloheptyl, cyclooctyl, and the like.

In the above general formula, R" represents the same groups as R, except that R cannot be a-hydrogen atom. When both R and R are lower-alkyl groups, they may be joinedto form together with the carbon atom bearingthe hydroxyl group a cycloalkyl ringer a lower-alkylatedwhere n is'an integer from 1 to 4, and lower'alkylated derivatives thereof, including such groups as 1-hydroxycyclopentyl, 1-hydroxy-2-methylcyclopentyl, l hydroxycyclohexyl, 1-hydroxy-4-methylcyclohexyl, l'hYdi'OXYCY! cloheptyl, l-hydroxycyclooctyl, and thelike.

Y represents a lower-alkylene group or bridge having Patented Aug. 15, 1961 the free valences on difierent carbon atoms, and preferably having from two to five carbon atoms, and thus Y includes the straight chain polymethylene radicals, (CH Where n is 2-5, and branched chain radicals including such groups as The N=B portion of the molecule stands for a tertiary-amino radical of the aliphatic or cycloaliphatic type and includes di-lower-alkylamino, polymethylenimino and morpholino radicals. The alkyl groups of the di-lower-a1kylamino radicals can be the same or different and each has less than about eight carbon atoms. The polyrnethylenimino radicals are simply cases where the alkyl groups of the di-lower-alkylamino groups are joined to produce a heterocyclic ring. The rings are 5- to 8 membered and thus include pyrrol'idino, piperidino, hexamethylenimino and heptamethylcnimino radicals and lower-alkylated derivatives thereof.

The new basic esters are prepared by catalytic reduction of the appropriate a-aryLB-hydroxy'alkamic acid, having the formula wherein Ar is phenyl or lower-alkyl-substituted phenyl, followed by esterifying the intermediate oi-CYClOhBXYl-fl hydroxyalkanoic acid having the formula R OH with the appropriate tertiary-aminoalkanol.

The required a-phenyl- -hydroxyalkanoic acid is prepared from the chloromagnesiurn derivative of the sodium or chloromagnesium salt of phenylacetic acid by the general procedureof D. Ivanov and A. Spassov, Bull. Soc. Chim. [4] 49, 377 (1931); and D. Ivanov and N. I Nicolov, ibid; [4] 51, 1325 (1932). In this process the chloromagnesium derivative of the salt of phenylacetic acid is reacted with a carbonyl compound R''CO'-R, and the intermediate organometallic complex is hydrolyzed'to pro duce the desired a-phenyl-fi hydroxyalkanoic acid. If a vcompound'is desired where one or both of R and R" is cyclohexyl it is convenient, although not prerequisite, to employ in the Ivanov reaction the corresponding carbonyl compound wherein one or both of R and R are'phenyl groups. Inithe subsequent catalytic hydrogenation reaction all of the phenyl groups are then'reduced to cyclohexyl groups. If a compound is desired where K is 'alkylated cyclohexy-l group, the Ivanov reaction is carried out with a ring alkylated phenylacetic" acid, for example, p-tolylacetic acid, 2,4-xylylacetic acid, and the like, followed by catalytic reduction of the aromatic ring. The esterification reaction is carried out by one of the following methods;

(1)" the acid, RRC(OH)--CH(R)COOH, is reacted with a tertiary-aminoalkanol, HO--Y--N=B, using a strong'min'eral acid such as sulfuric acid as a catalyst, present in an amount greater than that necessary to neutralize the amino alcohol. The sulfate or bisulfate-salt of the basic'ester is formed, and the tree basic ester canb'e' obtained'by addition of alkali to the reactionmixture; (2) The" acid, RRC(OH)CH(R)-COOH, is"

heated with a tertiary-aminoalkyl' halide of the formula Z'Y-N=B, where Z is halogen (preferably chlorine or bromine). The temperature at which the reactants are heated is preferably between about 50 C. andl50 C. A hydrohalide of thebasic ester is obtained which can" be converted to the free basic ester by the addition of alkali to the reaction mixture.

(3) A metallic salt of the acid,

is heated or simply mixed with a tertiary-aminoalkyl halide, ZY-N=B, where Z is halogen. In this case the free basic ester is formed directly.

These new basic esters are most conveniently used in the form of water-soluble, non-toxic acid-addition or quaternary ammonium salts and these salts are within the purview of the invention. The acids which can be used to prepare acid-addition salts are preferably those which produce when combined with the free base, salts whose anions are relatively innocuous to the animal organism in therapeutic doses of the salts, so that the beneficial physiological properties inherent in the free base are not vitiated by side efiects ascribable to the V aralkyl esters of inorganic acids or organic sulfonic acids,

including such compounds as methyl chloride, methyl bromide, methyl iodide, ethyl bromide, propyl bromide, benzyl chloride, benzyl bromide, methyl sulfate, methyl benzenesulfonate, and methyl p-toluenesulfonate, giving the methochloride, methobromide, methiodide, ethobromide, propobromide, benzochloride, benzobromide, methosulfate, methobenzenesulfonate and metho-p-toluenesulfonate salts, respectively.

The following examples will further illustrate the invention.

EXAMPLE 1 (a) a-Cyclohexyl-fl-hydroxyvaleric acid (Ri H R'=H, R"=C H ).-u-Phenyl-fi-hydroxyvaleric acid (4.85 g., 0.025 mole), M.P. 141142 (3., was dissolved in 60 ml. of glacial acetic acid and 0.3 g. of platinum oxide catalyst was added. The mixture was hydrogenated under an initial pressure of 50 lbs. per sq. inch until the calculated amount of hydrogen had been absorbed. The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure on a steam bath. The residue was recrystallized from benzene, giving 4.15 g. (83%) of a-phenyl-fl-hydroxyvaleric acid, M.P. 99- 101 C.

Neut. Equiv. Calcd.: 200.3. Found: 200.0. Analysis.-Calcd. for C H O I C, 65.97; H, 10.07. Found: C, 65.82; H, 10.43.

(b) fl-Diethylaminoethyl or cyclohexyl ,8 hydroxyvalerate-a-Cyclohexyl-fl-hydroxyvaleric acid (8.0 g., 0.04 mole), prepared as described above in part (a), was dissolved in 50 ml. of isopropyl alcohol. To this solution, which was kept under reflux, was added dropwise over a period of about two hours 5.35 g. (0.04 mole) of fl-diethylaminoethyl chloride, which had previously been dissolved in its own weight of anhydrous benzene. The reaction mixture was refluxed for an additional eight hours, and then was filtered while hot to remove the small amount of tetraethylpiperazinium dichloride which formed during the course of the reaction. The cooled solution was diluted with ether until precipitation of the ester hydrochloride was initiated, and then cooled overnight in a refrigerator. The product was collected by filtration, washed with ether and recrystallized from methyl ethyl ketone, giving 8.0 g. (59%) of fl-diethylaminoethyl a-cyclohexyl-fi-hydroxyvalerate in the form of its hydrochloride salt, M.P. 103-105 C.

Analysis.Calcd. for C H O NCI: C, 60.78; H, 10.21; Cl, 10.55. Found: C, 61.07; H, 10.50; Cl, 10.48.

A portion of the above hydrochloride salt was converted to the free base, fl-diethylaminoethyl a-cycl ohexylfl-hydroxyvalerate, by treatment of the hydrochloride with dilute aqueous sodium hydroxide solution and extracting the free base with ether. To the ether solution of the free base was added an excess of methyl bromide and the solution was allowed to stand at room temperature until a crystalline product had formed. The latter was collected by filtration and recrystallized from an isopropyl alcohol-methyl ethyl ketone mixture, giving 5- diethylaminoethyl a-cyclohexyl-fi-hydroxyvalerate in the form of its methobromide salt, M.P. -126 C.

Analysis.-Calcd. t or C H O NBr: C, 54.81; H, 9.20; N, 3.55; Br, 20.27. Found: C, 55.16; H, 9.10; N, 3.58; Br, 20.12.

EXAMPLE 2 (a) ot-cyclohexyl-fi-hydroxycaproic acid (R=C H R'=H, R=(CH 'CH was prepared by catalytic hydrogenation of a-phenyl- 3-hydroxycaproic acid, M.P. 155156 C., by the manipulative procedure described above in Example 1, part (a). a-Cyclohexyl-fl-hydroxycaproic acid was obtained in 76% yield and had the M.P. 99-100 C. when recrystallized from benzene.

Neut. Equiv. Calcd.: 214.3. Found: 213.4.

Analysis.-Calcd. for C H O C, 67.25; H, 10.35. Found: C, 67.00; H, 10.23.

(b) B-Diethylaminoethyl a cyclohexyl )3 hydroxycaproate was prepared by esten'fication of a-cyclohexylfl-hydroxycaproic acid with B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl a-cyclohexylp-hydroxycaproate was obtained in the form of its hydrochloride salt in 55% yield, M.P. 100;-102 C. when recrystallized from a methyl ethyl ketone-ether mixture.

' Analysis.-Ca1cd. for C H O NCl: C, 61.78; H, 10.37; N, 4.00; Cl, 10.14. Found: C, 61.68; H, 10.51; N, 3.98; Cl, 10.14.

The minimum effective concentration (ED of B-diethylaminoethyl a-cyclohexyl-fi-hydroxycaproate hydrochloride as an antispasmodic against acetylcholine spasms induced in the isolated intestine was about 1 part in 3,800,000.

B-Diethylaminoethyl a cyclohexyl-B-hydroxycaproate was obtained in the form of its methobromide salt, which had the M.P. 121-l22 C. when recrystallized from an isopropyl alcohol-methyl ethyl ketone mixture.

- Analysis.--Calcd. for C H O NBr: C, 55.87; H, 9.38; N, 3.43; Br, 19.57. Found: C, 55.88; H, 9.52; N, 3.41; Br, 19.43.

The ED value of ,B-diethylaminoethyl wcyclohexylfi-hydroxycapnoate methobromide as an antispasmodic was found to be about 1 part in 26,000,000.

EXAMPLE 3 (a) a-Cyclohexyl-fl-hydroxybutyric acid (R=C H R'=H, R"=CH was prepared by catalytic hydrogenation of a-phenyl-fl-hydroxybutyric acid, M.P. -136" C., by the manipulative procedure described above in Example 1, part (a). a-Cyclohexyl- 3-hydroxybutyric acid was obtained in 84% yield and had the M.P. 142 C. when recrystallized from toluene.

Neut. Equiv. Calcd.: 186.2. Found: 186.7.

Analysis.Calcd. for C H O C, 64.49; H, 9.74. Found: C, 64.80; H, 9.56.

(b) B Diethylaminoethyl a cyclohexyl-fl-hydroxybutyrate was prepared by esterification of a-cyclohexyl-flhydroxybutyric acid with 13-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl a-cyclohexylfl-hydroxybutyrate when reacted with methyl iodide was obtained in the form of its methiodide salt, which had the M.P. 9295 C. when recrystallized from an ethyl alcoholethyl acetate mixture.

Anaiysis.-Calcd. for C H O NI: C, 47.77; H, 8.02; N, 3.28; I, 29.70. Found: C, 47.59; H, 7.97; N, 3.23; I, 29.54.

EXAMPLE 4 (a) a Cyclohexyl B hydroxy-y-methylvaleric acid (R=C H R'=H, R=CH(CH was prepared by catalytic hydrogenation of aphenyl-B-hydroxy-'y-methy1- valeric acid, M.P. 126-127 C., by the manipulative procedure described above in Example 1, part (a). OL-CYCIO- hexyl-fl-hydroxy-'y-methylvaleric acid was obtained in 79% yield and had the M.P. 119-121" C. when recrystallized from benzene.

Neut. Equiv. Calcd.: 2.14.3. Found: 2.14.8.

Analysis.--Calcd. for C H O C, 67.25; H, 10.35. Found; C, 67.55; H, 10.49. V

(b) fl-Diethylaminoethyl a-cyclohexyl-ji-hydroxy-vmethylvalerate was prepared by esterification of u-cyclohexyl-fl-hydroxy 'y-methylvalerie acid with- B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethy1- aminoethyl a-cyclohexyl-fi-hydroxy y-methylvalerate was obtained in the form of its hydrochloride salt in 66% yield, M.P. 139-141" C. when recrystallized from an isopropyl alcohol-acetone mixture.

Analysis.-Calcd. for C H O NCl: C, 61.78; H, 10.37; N, 4.00; Cl, 10.14. Found: C, 61.72; H, 10.44; N, 3.98; Cl, 10.28.

The ED value of B-diethylaminoethyl u-cyclohexyl- B-hydroxy-y-methylvalerate hydrochloride as an antispasrnodic was found to be about 1 part in 2,100,000.

B Diethylaminoethyl a-cyclohexyl-fl-hydroxy-v-methylvalerate was obtained in the form of its methobromide salt, which had the M.P. 190-192 C. (dec.) when recrystallized from an isopropyl alcohol-acetone mixture.

Analysis.Calcd. for C H O NBr: C, 55.87; H, 9.38; N, 3.43; Br, 19.57. Found: C, 55.74; H, 9.36; N, 3.39; Br, 19.46.

The ED value of B-diethylaminoethyl a-cyclohexyl-flhydroxy- -methylvalerate methobromide as an antispasmodic was found to be about 1 part in 7,400,000.

EXAMPLE 5 (a) a-Cyciohexyl-B-hydroxypelargonic acid (R=C H R'=H, R "=(CH CH was prepared by catalytic hydrogenation of a-phenyl-fi-hydroxypelargonic acid, M.P. 109110 C., by the manipulative procedure described above in Example 1, part (a). u-Cyclohexyl-fl-hydroxypelargonic acid was obtained in 81% yield and had the M.P. 93-94" C. when recrystallized from toluene.

\Neut. Equiv. Calcd.: 256.4. Found: 256.1.

Analysis--Calcd. for C H O z C, 7027; H, 11.01. FoundrC, 70.39; H, 11.25.

(b) ,8 Diezfhylaminoethyl a-cyclohexyl-fi-hydroxypelargonate was prepared by esterification of ot-cyclohexyl=fi-hydroxypelargonic acid with fl-diethylaminoethyl. chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl a-cyclohexyl-fi-hydroxypelargonate was obtained in the form of its hydrochloride salt in 68% yield, M.P. 109- 111 C; when recrystallized from methyl ethyl ketone.

AnalysiLs'J-Calcd. for C H O NC'l: C, 64.34; H, 10.80; N, 3.57; Cl, 9.04. Found: C, 64.43; H, 10.77; N, 3.61; Cl, 8.95.

,B- Diethylaminoethyl u-cyclohexyl ,8 hydroxypelargonate was obtained in the form of its .methobromide salt, which had the MP. 1'00-103 C. when recrystallized from an isopropyl alcohol-ether mixture.

A-nalysis.-Calcd. for C H O NBr: C, 58.65; H, 9.85; N, 3 .11;, Br,,17.74. Found: C, 58.37; H, 9.84; N, 3.08; Br, 17.65.

EXAMPLE 6 (a) ot-Cyclohexy- 3 hydroxytoaprylic acid (R=C H R'=H, R"=(CH CH was prepared by catalytic hydrogenation ofa p'henyl-pdiydroxycaprylic acid, M.P.

110-111 C., by the manipulative procedure described above in Example 1, part (a). ot-Cyclohexyl-B-hydroxycaprylic acid was obtained in 88% yield and had the M.P. 98-99 C. when recrystallized from benzene.

Neut. Equiv. Calcd.: 242.3. Found: 241.5.

Analysis.Calcd. for C H O C, 69.38; H, 10.81. Found: C, 69.28; H, 10.71.

(b) 5 Diethylaminoethyl a-cyclohexyl-fl-hydroxycaprylate was prepared by esterification of ot-cyclohexyl-B- hydroxycaprylic acid with B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl a-cyclohexyl- B-hydroxycaprylate was obtained in the form of its hydrochloride salt in yield, M.P. -107 C. when recrystallized from methyl ethyl ketone.

Analysis.-Calcd. for C H O NC1: C, 63.54; H, 10.67; N, 3.71; Cl, 9.38. Found: C, 63.56; H, 10.82; N,

B Diethylaminoethyl a-cyclohexyl-{i-hydroxycaprylate was obtained in the formof its methobrornide salt, which had the M.P. 101-103 C. when recrystallized from an acetone-ether mixture.

Analysis.-Calod. for C H' O Nl3r: C, 57.78; H, 9.70; N, 3.21; Br, 18.31. Found: C, 58.03; H, 9.91; N, 3.19; Br, 18.10;

EXAMPLE 7 (a) a,fi- Dicyclohexyl t3 hydroxypropionic acid (R=C H R'=H, R"=C H was prepared by catalytic hydrogenation of u,fi-diphenyl-fl-hydroxypropionic acid, M.P. 173174 C. by the manipulative procedure described above in Example 1, part (a), except that the reduction was allowed to continue until suificient hydrogen had, been taken up to reduce both phenyl rings. a, 3-Dicyclohexyl-B-hydroxypropionic acid was obtained in 89% yield and had the M.P. 184186 C. when recrystallized from toluene.

Neut. Equiv. Calcd.: 254.4. Found: 253.4.

Analysis.-Calcd. for C H O C, 70.82; H, 10.30. Found: C, 70.63; H, 10.02.

(b) fi-Diethylaminoethyl a,fl-dicyclohexyl-B-hydroxypropionate was prepared by esterification of mfl-dicyclohexyl-B-hydroxypropionic acid with ,l'3-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl 11,18 dicyclohexyl-fl-hydroxypropionate was obtained in the form of its hydrochloride salt in 80% yield, M.P. 166- 168 C. when recrystallized from isopropyl alcohol.

Analysis.-Calcd. for C H O NCl: C, 64.68; H, 10.34; N,,3.59; Cl, 9.09. Found: C, 64.53; H, 10.50; N, 3.55; Cl,.8.98.

The ED value of fl-diethylarninoethyl a,B-dicyclohexyl-B-hydroxypropionate hydrochloride as an antispasmodic was found to be about 1 part in 1,800,000.

B-Diethylaminoethyl fi-dicyclohexyl ti hydroxypropionate was obtained in the form of its methobromide' salt, which had the M.P. -138 C. when recrystallized from an ethyl alcohol-ether mixture.

A'nalysis-Ca-lcd. for C H O NBr: C, 58.92; H, 9.44; N, 3.12; Br, 17.82. Found: C, 58.90; H, 9.50; N, 3.08; Br, 17.78.

EXAMPLE 8 hexyl-fi-hydroxy-fl-methylbutyric acid was obtained in.

93% yield and had the M.P. 105-106" C. when recrystallized from benzene.

NeutaEquiv. Calcd.: 200.3. Found: 200.6.

Analysis.-Calcd. for C H O C, 65.97; H, 10.07.:

Found: C, 65.76; H, 10.14.

(b)- ,B-Diethylaminoethyl oi-cyclohexyi- [3 hydroxy-B- me'thylbutyrate was prepared by esterification of u-cyclohexyl-p-hydroxy-;8-methylbutyric acid with p-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). ,B-Diethylaminoethyl a-cyclohexyl-p-hydroxy-fl-methylbutyrate was obtained in the form of its hydrochloride salt in 76% yield, M.P. 139-141 C. when recrystallized from an isopropyl alcohol-methyl ethyl ketone mixture.

Analysis.--Calcd. for C17H34O3INCII C, 60.78; H, 10.21; N, 4.17; Cl, 10.55. Found: C, 61.16; H, 10.35; N, 4.14; Cl, 10.47.

The ED value of ,B-diethyl-aminoethyl a-cyclohexyl-B- hydroxy-p-methylbutyrate as an antispasmodic was found to be about 1 part in 2,500,000.

8-Diethylaminoethy1 a-cyclohexyl-B-hydroxy-B-methylbutyrate was obtained in the form of its methobromide salt, which had the M.P. 128130 C. when recrystallized from acetone.

Analysia Calcd. for C H O NBr: C, 54.81; H, 9.20; N, 3.55; Br, 20.27. Found: C, 55.02; H, 9.17; N, 3.57; Br, 20.18.

EXAMPLE 9 (a) a-Cyclohexyl {3 hydroxy ,8 ethylvaleric acid (R=C H R=C H R"=C H was prepared by catalytic hydrogenation of a-phenyl-fi-hydroxy-B-ethylvaleric acid, M.P. 151-152 C. by the manipulative procedure described above in Example 1, part (a). a-Cyelohexylp-hydroxy-B-ethylvaleric acid was obtained in 82% yield and had the M.P. 84-86 C. when recrystallized from benzene.

Neut. Equiv. Calcd.: 228.3. Found: 229. 1.

Analysis.-Calcd. for C H O C, 68.39; H, 10.59. Found: C, 68.37; H, 10.56.

(b) ,B-Diethylaminoethyl a-cyclohexyl ,8 hydroxy-flezhylvalerate was prepared by esterification of oc-cyclohexyl-p-hydroxy-B-ethylvaleric acid with B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl a-cyclohexyl-B-hydroxy-p-ethylvalerate was obtained in the form of its hydrochloride salt in 68% yield, M.P. 129-131 C. when recrystallized from an isopropyl alcohol-ether mixture.

Analysis.Calcd. for C H O N'Cl: C, 62.69; H, 10.53; N, 3.85; Cl, 9.74. Found: C, 62.62; H, 10.78; N, 3.81; Cl, 9.71.

p-Diethylaminoethyl OL-CYClOhBXYl fi-hydroxy-fi-ethylvalerate was obtained in the form of its methobromide salt, which had the M.P. ISO-152 C. when recrystallized from acetone.

Analysis.Calcd. for C H O -NBr: C, 56.87; H, 9.54; N, 3.31; Br, 18.92. Found: C, 56.63; H, 9.54; N, 3.34; Br, 18.78.

EXAMPLE (a) a-Cyclohexyl 5 hydroxy 3 methylvaleric acid (R=C H R'=C H R"=CH was prepared by catalytic hydogenation of a u-phenyl-fi-hydroxy-B-methylvaleric acid, M.P. 9294 C. by the manipulative procedure described above in Example 1, part (a). a-Cyclohexyl-B-hydroxy-B-methylvaleric acid was obtained in 72% yield and had the M.P. 8990 C. when recrystallized from a benzene-petroleum ether (B.P. 60-75 C.) mixture.

Neut. Equiv.Calcd.: 214.3. Found: 214.7.

Analysis.-Calcd. for C H O C, 67.25; H, 10.35. Found: C, 67.46; H, 10.46.

(b) B-Diethylaminoethyl tat-cyclohexyl 13 hydroxy-fimethylvalerate was prepared by esterification of a-cyclohexyl-B-hydroxy-B-methylvaleric acid with B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). fl-Diethylaminoethyl a-cyclohexyl-,6-hydroxy-fl-methylvalerate was obtained in the form of its hydrochloride salt in 67% yield, M.P. 1161l7 C. when recrystallized from methyl ethyl ketone.

' Analysis.-Calcd. for C H O NCl: C, 61.78; H,

-8 10.37; N, 4.00; Cl, 10.14. Found: C, 61.74; H, 10.53; N, 4.02; CI, 10.08.

fl-Diethylarninoethyl a-cyclohexylfi-hydroxy-fi-methylvalerate was obtained in the form of its methobromide salt, which had the M.P. 142144 C. when recrystallized from an ethyl alcohol-ether mixture.

Analysis.Calcd. for C H O NB1': C, 55.87; H, 9.38; N, 3.43; Br, 19.57. Found: C, 55.80; H, 9.42; N, 3.41; Br, 19.36.

EXAMPLE 11 (a) a,[3-Dicyclohexyl-B-hydroxybutyric acid (R=C H R'=CH R"=C H was prepared by catalytic hydrogenation of u,;3-diphenyl-B-hydroxybutyric acid, M.P. 187 C. by the manipulative procedure described above in Example 1, part (a), except that the reduction was allowed to continue until sufiicient hydrogen had been taken up to reduce both phenyl rings. a,B-Dicyclohexyl-fi-hydroxybutyric acid was obtained in 72% yield and had the M.P. 141-143 C. when recrystallized from toluene.

Neut. Equiv. Calcd.: 268.4. Found: 268.0.

Analysis.-Calcd. for C H O C, 71.60; H, 10.52. Found: C, 71.35; H, 10.60.

(b) B-Diethyldminoethyl a,fl-dicycl0hexyl-fl-hydroxybutyrate was prepared by esterification of a,fl-dicyclohexylfl-hydroxybutyric acid with ,B-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, pant (b). fl-Diethylaminoethyl a,fl-dicyclohexyl-p-hydroxybutyrate was obtained in the form of its hydrochloride salt in 66% yield, M.P. 147-149 C. when recrystallized from methyl ethyl ketone.

Analysis.Calcd. for C H O NCI: C, 65.40; H, 10.48; N, 3.47; CI, 8.77. Found: C, 65.44; H, 10.44; N, 3.46; Cl, 8.89.

p-Diethylaminoethyl a,B-dicyclohexyl fi-hydroxybutyrate was obtained in the form of its methobromide salt, which had the M.P. 194-195" C. (dec.) when recrystallized from an ethyl alcoholether mixture.

Analysis.Calcd. for C H O Nl3r: C, 59.72; H, 9.59; N, 3.03; Br, 17.28. Found: C, 59.42; H, 9.68; N, 2.97; Br, 17.15.

EXAMPLE 12 (a) a-Cyclohexyl 5 hydroxy-fi-propylcaproic acid (R=C H R'=C H R"=C H-,) was prepared by catalytic hydrogenation of a-phenyl-/3-hydroxy-fl-propylcaproic acid, M.P. 176177 C. by the manipulative procedure described above in Example 1, part (a). a-Cyclohexylfi-hydroxy-fi-propylcaproic acid was obtained in 91% yield and had the M.P. 116-118 C. when recrystallized from benzene.

Neut. Equiv. Calcd.: 256.4. Found: 255.4.

Analysis.-Calcd. for C H O C, 70.27; H, 11.01. Found: C, 70.59; H, 10.97.

(b) ,B-Diethylaminoethyl tat-cyclohexyl ,B hydroxyfl-propylcaproate was obtained by esterification of a-cyclohexyl-B-hydroxy-fi-propylcaproic acid with fi-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). fl-Diethylaminoethyl 0c cyclohexyl ,B-hydroxy-fi-propylcaproate was obtained in the form of its hydrochloride salt in 67% yield, M.P. 123125 C. when recrystallized from methyl ethyl ketone.

' Analysis.Calcd. for C H O NCl: C, 64.34; H, 10.80; N, 3.57; CI, 9.04. Found: C, 64.48; H, 10.83; N, 3.56; Cl, 8.98.

S-Diethylaminoethyl OL-CYCiOhCXYl fi-hydroxy-fi-propylcaproate was obtained in the form of its methobromide salt, which had the M.P. 183-185 C. when recrystallized from an ethyl alcoholisopropyl alcohol mixture.

Analysis.-Calcd. "for C H O NBr: C, 58.65; H, 9.85; N, 3.11; Br, 17.74. Found: C, 58.80; H, 10.07; N, 3.07; Br, 17.59.

EXAMPLE 13 (a) a cyclohexyl a (I-hydroxycyclopentyl)acetic acid; s n, 4 and RE" 2( 2)2 2) was prepared by catalytic hydrogenation of a-phenyl-a(.1 hydroxycyclopentyl) acetic acid, M.P. 99-100 C. by the manpulative procedure described above in Example 1, part (a). u-Cyclohexyl-u (l-hydroxycyclopentyl)acetic acid. was obtained in 66% yield and had the M.P. 109- 110 C. when recrystallized. from a toluene-petroleum ether (B.P. 60-75 C.) mixture.

Neut. Equiv. Calcd: 226.3. Found: 226.7.

Analysis.Calcd. for C H O C, 68.99; H, 9.80. Found: C, 68.91; H, 10.01.

(b) ,8 Diethylaminoethyl.arcyclohexyl a-(l-hydroxycyclopentyl)-acetate was prepared by esterification of ozcyclohex-yl u (l-hydroxycyclopentyl)acetic acid. with fl-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). B- Diethylaminoethyl a-cyclohexyl-a (l-hydrocyclopentyl) acetatewas obtained in the form of its hydrochloride salt in 41% yield, M.P. 125-128 C. when recrystallized from an n-butyl alcohol-ether mixture. I

Analysis.-Calcd. for C H O NCl: C, 63.04; H, 10.03; N, 3.87; Cl, 9.80. Found: C, 63.15; H, 10.07; N, 4.09; C1, 1001.

B-Diethylaminoethyl a cyclohexyl-a-(l-hydroxycyclopentyl) acetate hydrochloride was found to have an ED value as an antispasmodic of about 1 part in 32,000,000.

fieDiethylaminoethyl oz cyclohexyl u-(l hydroxycyclopentyl)acetate was obtained in the form, of its methobromide salt, which had the M.P. 112-114 C. when-re crystallized from an ethyl acetate-ether mixture.

Analysis.-Calcd. for C H O NBr: C, 57.15; H, 9.10; N, 3.33; Br, 19.02. Found: C, 56.89; H, 9.23; N, 3.27; Br, 19.20.

fieDiethylaminoethyl oz cyclohexyl-u-(l-hydroxycyclopentyl)'acetate methobromide was found to have an ED value as any antispasmodic of about 1 part in 93,000,000.

EXAMPLE 14 (a) ot-Cyclohexyl a (J hydroxycyclohexyDacetic 4. 4 6 lh an R" *CH2(.CH2)3C.H2 Was prepared by catalytic hydrogenation of a-phenyl- -(L, hydroxycyclohexyDacetic acid, M.P. 139-140 C. by the manipulative procedure described above in Example 1,

(a), o -Cyclohexyl oc (1 hydroxycyclohexyD- acetic acid was obtained'in 85% yield and had. the M.P'. 1 52 -l5 4 C. when recrystallized from toluene.

Neut. Equiv. Calcd.: 2.40.4. Found: 239.3. 7

Anulysia-Caled. for C I-1 ,0 C; 69.97; H, 10.07. Found; C, 70.13; H, 10.09.

(b) g Diethylaminoe thyl oz-cyclohexyl-a-(I-hydroxycycIOhexyD-acetate was prepared by esterification ofacyclohexyl a (1-hydroxycyclohexyl)acetic acidwith fldiethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). fl-diethylaiminoethylh-cyclohexyl a (I-hydroxycyolohexyl) ace tate was obtained in the form of its hydrochloride salt in 82% yield, M .P. 176-178 "C; when recrystallizedfrom isopropyl alcohol.

Analysis.-Calcd: for C H O NCl: C, 63189; H, 10.19; 11,3273; Cl; 9.43. Found; C, 63.92; H; 10.42; N, 3.70; C1, 9.37.

B=Diethylaminoethyl 0c cyclohexyl a (1-hydr0xy-. cyolohexyl) acetate was found to have an ED value as an antispasmodic'of about 1 part in 6,500,000.

fi-Diethylaminoethyl a. cyclohexyl-a-(l-hydroxycyclohexyDacetate was. obtained in. the. formof its methobromide sa1t, which had the M.P. 136-1-38 'C. when,re-. crystallized from an. ethyl alcohol-ether mixture.

Analysis.-Calcd. for C H OgNBr: C, 58.05; H,- 9.2.8.; N, 3.22; Br, 18.40. Found: C, B15, 1829. 1

.B-Diethylaminoethyl co cyclohexyl a 1 -hydroxyantispasmodic of about 1 part in 42,000,000.

. IQ. EXAMPLE 15 'y-Dimethylaminopropyl oz cyclohexyla (1 -hydroxy.- cyclohexyl.)acetate was prepared by esterification of mcyclohexyl a (1-hydroxycyclohexyl)acetic acid with-1w dimethylaminopropyl. chloride according to the manipulative procedure given above in Example 1, part (b). 'y- Dimethylaminopropyl'arcyclohexyl a (l-hydroxycyolohexyl) acetate was obtained in the form of its hydrochloride salt in 64% yield, M.P. 151-153 C. when recrystal lized from an isopropyl alcohol-methyl ethyl ketone mixtum.

Analysis.-Calcd. for C H O NCl: C, 63.05; H, 10.02; N, 3.87;, Cl, 9.80. Found: C, 62.80; H, 10.09; N, 3.89; Cl, 9.71.

EXAMPLE 16 fi-Piperidinoethyl on. cyclohexyl a (l-h'ydroxycyclohexyl)acetate was prepared by esterification of a-cyclohexyl. a (1 hydroxycyclohexyl) acetic acid with {3 piperidiuoethyl chloride according to the manipulative pro; cedure given above in Example 1, part (b). B-Piperidino! ethyl cc-CYClOhteXYl- -u-(l, hydroxycyclohexyl)acetate was obtained in the form of its hydrochloride salt in 77% yield; M.P. 195-196 C. when recrystallized from isopropyl alcohol-methyl ethyl ketone.

A-nalysis.Cal cd; for C H O NCl: C, 65.01; H, 9.87; N, 3;.61; Cl, 9.14. Found: C, 65.07; H, 10.03; N, 3.57; Cl, 9.01.

EXAMPLE 17 (a) u cyclohexyl-a-(1-hydroxy-4-methylcyclohexyl)- acetic-acid (R =C H R and R: -CH CH CH(CH )CH CH' was prepared by catalytic hydrogenation of a-pheny l-a- (1-hydroxy-4-methylcyclohexyl) acetic acid, M.P. 177'- 178 C., by the manipulative procedure described above in Example 1, part a). a-Cyclohexyl-u-(1-hydroxy-4- methylcycloheXy-Dacetic acid Was obtained in 73% yield and had the M-.P; 159-160 C. when recrystallized from a methyl ethy lketone-petroleum ether (B.P. -75" C.)- mixture Neut. Equiv. Calcd.: 254.4. Found: 254.0.

Analysis-Calm. for C I-1 0 C, 70.82; H, 10.30. Found: C, 70.83; H, 10.41.

(b') 13-Diethylaminoethyl ot-cycl0hexyl-a-(1-hydr0xy-4- methylcyclqhexyl)ac etate was prepared by esterificat-ion of a-cyclohexyl-a- 1-hydroxy-4-methylcyclohexyl acetic. acid-with fl-diethylamino ethyl chloride according to the manipulative procedure given above in Example 1, part (b); fl-Diethylaminoethyl a-cyclohexyl-a-(l-hydroxy-4- methylcyclohexyl)ac etate was obtained in the form of its hydrochloride salt in 77% yield, M.P. 183-185 C. when recrystallized; from isopropyl alcohol.

AnalySis.Ca1cd. for C21H4003NC1: 10.34; N, 3.59; Cl, 9.09. Found: C, 64.69; H, 10.25; N, 3 .55; CI, 9.16.

,8 Diethylaminoethyl a cyclohexyl a (l-hydroxy-4- methylcyclohexyl)acetate hydrochloride was found to have-an ED value as an antispasmodic of about 1 part 18 -,Diethylam-inoethyl a cyclohexyl-a-(l-hydroxy 4- methylcyclohexyhacetate was obtained in the form of its methobromide salt, which had the M.P. 155157 C.,

when recrystallized from an acetone-ether mixture.

Analysis.-Calcd. for C H O NBr: C, 58.92; H, 9.44;

N, 3.12; Br, 17.82. Found: C, 59.20; H, 9.42; N, 3.07;.

1 have an ED value as an antispasmodic of about 1 part EXAMPLE 18 (a) a Cyclohexyl (1-hydr0xy3-methylcyclohexyl)-,

acetic acid; (R=C H R and R": -CH CH(CH )CH CH CH was prepared by catalytic hydrogenation of a-phenyl-a- (1-hydroxy-3-methylcyclohexyl)acetic acid, M.P. 194- 195' C. by the manipulative procedure described above in Example 1, part (a). a-Cyclohexyl-a-(l-hydroxy-B-methylcyclohexyl)acetic acid was obtained in 71% yield and had the M.P. 142144 C. when recrystallized from methyl ethyl ketone.

Neut. Equiv. Calcd: 254.4. Found: 254.9. Analysis.-Calcd. for C H O C, 70.82; H, 10.30. Found: C, 70.63; H, 10.36.

(b) [ii-Diethylaminoethyl a-cyclohexyl-ot- Lhydroxy-S- methylcyclohexybacetaie was prepared by esterification of a cyclohexyl-a-( 1-hydrox'y-3-methylcyc1ohexyl) acetic acid with fi-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). ti-Diethylaminoethyl acyclohexy1-a-(1-hydroxy-3- methylcyclohexyl)acetate was obtained in the form of its hydrochloride salt in 68% yield, M.P. 159-161" C. when recrystallized from methyl ethyl ketone.

, Analysis.Calcd. for C H O NCl: C, 64.68; H, 10.34; N, 3.59; CI, 9.09. Found: C, 64.78; H, 10.35; N, 3.57; Cl, 9.01.

B Diethylaminoethyl a cyclohexyl a-(1-hydroxy-3- methylcyclohexyl)acetate was obtained in the form of its methobromide salt, which had the M.P. 149-151" C. when recrystallized from an ethyl alcohol-ether mixture.

Analysis.Calcd. for C H O NBr: C, 58.92; H, 9.44; N, 3.12; Br, 17.82. Found: C, 58.67; H, 9.65; N, 3.08; Br, 17.63.

EXAMPLE 19 (a) a-cyclohexyl-d-(I-hydroxycycloheptyl)acetic acid (R=C H R and R: CH (CH CH was prepared by catalytic hydrogenation of a-phenyl-a-( l-hydroxyoycloheptyl)acetic acid, M.P. 148 C., by the manipulative procedure described above in Example 1, part (a). a-Cyclohexy1-a-(l-hydroxycycloheptyl)acetic acid was obtained in 63% yield and had the M.P. l22-l24 C. when recrystallized from a toluene-petroleum ether (B.P. 60-75 C.) mixture.

Neut. Equiv. Calcd.: 254.4. Found: 252.6.

Analysis.Calcd. for C I-[ C, 70.82; H, 10.30. Found: C, 70.82; H, 10.38.

(b) ,6 Diethylaminoethyl a-cyclohexyl-m-(l-hydroxycycloheptyl)-acetate was prepared by esterification of a-cyclohexyl-a-(l-hydroxycycloheptyl)acetic acid with fl-diethylaminoethyl chloride according to the manipulative procedure given above in Example 1, part (b). p Diethylaminoethyl a cyclohexyl tX-( l-hydroxycycloheptyl)acetate was obtained in the form of its hydrochloride salt in 40% yield, M.P. 195-197 C. when recrystallized from an n-butyl alcohol-ether mixture.

Analysis-Calm. for C H O NCl; C, 64.68; H, 10.34; N, 3.59; Cl, 9.09. Found: C, 64.71; H, 10.36; N, 3.64; CI, 9.02.

,B-Diethylaminoethyl a-cyclohexyl-a-(l-hydroxycycloheptyl)acetate hydrochloride was found to have an ED value as an antispasmodic of about 1 part in 7,500,000.

13 Diethylaminoethyl a-cyclohexyl-u-( l-hydroxycycloheptyl)acetate was obtained in the form of its methobromide salt, which had the M.P. 139-141 C. when recrystallized from ethyl alcohol.

Analysis.Calcd. for C H, O NBr: C, 58.91; H, 9.44; N, 3.12; Br, 17.82. Found: C, 58.76; H, 9.46; N, 2.98; Br, 17.95.

B Diethylaminoethyl a-cyclohexyl-u-( l-hydroxycycloheptyl)acetate methobromide was found to have an ED value as an antispasrnodic of about 1 part in 45,000,000.

EXAMPLE 20 (a) a Cyclohexyl-u-(I-hydroxycyclooctyl)acetic acid (R=CHu, R and R":-

Was prepared by catalytic hydrogenation of a-phenyl-a-(l-hydroxycyclooctyl)acetic acid, M.P. 162-163 C., by the manipulative procedure described above in Example 1,

part (a). a-Cyclohexyl-u-(l-hydroxycyclooctyl) acetic acid was obtained in 67% yield and had the M.P. 147- 149 C. when recrystallized from toluene.

Neut. Equiv. Calcd: 268.4. Found: 268.0.

Analysis.Calcd. for C H O C, 71.60; H, 10.52.

Found: C, 71.53; H, 10.53. (b) p Diethylaminoethyl u-cyclohexyl-a-(l-hydroxycyclooctyl)-acetate was prepared by esterification of ozcyclohexyl-a-(l-hydroxycyclooctyl)acetic acid with fl-diethylaminoethyl chloride according the the manipulative procedure given above in Example 1, part (b). B-Diethylaminoethyl oz oyclohexyl-a-(1-hydroxyclooctyl)acetate was obtained in the form of its hydrochloride salt in 74% yield, M.P. -176 C. when recrystallized from isopropyl alcohol.

Analysis.Calcd. for C H O NCl: C, 65.40; H, 10.48; N, 3.47; Cl, 8.77. Found: C, 65.18; H, 10.25; N, 3.46; Cl, 8.75.

,9 Diethylaminoethyl u-cyclohexyl-a-( l-hydroxycyclooctyl)acetate was obtained in the form of its methobromide salt, which had the M.P. 139-142 C. when recrystallized from an isopropyl alcohol-ether mixture.

Analysis.-Calcd. for C H O NBr: C, 59.72; H, 9.59; N, 3.03; Br, 17.28. Found: C, 59.49; H, 9.65; N, 3.06; Br, 17.12.

EXAMPLE 21 (a) u,fl,fl-Tricyclohexyl fl hydroxypropionic acid (R=C H R'=C H R"=C H can be prepared by catalytic hydrogenation of a,B,,B-triphenyl-B-hydroxypropicnic acid, M.P. 206-207" C. by the manipulative precedure described above in Example 1, part (a), allowing for uptake of hydrogen sufficient to reduce all three phenyl groups.

' (b) p-Morpholinoethyl a,fi, 3-tricycl0hexyl-fl-hydroxypropionate can be prepared by esterification of oz,fl,}3- tricyclohexyl-B-hydroxypropionic acid with fl-morpholinoethyl chloride according to the manipulative procedure given above in Example 1, part (b).

EXAMPLE 22 (a) a-Cyclohexyl-fl-hydroxy-p-isopropyl-y-methylvaleric acid (R=C H R'=CH(CH R"=CH(CH can be prepared by catalytic hydrogenation of a-phenylp-hydroxy-p-isopropyl-y-methylvaleric acid, M.P. 156- 157 C. by the manipulative procedure described above in Example 1, part (a).

(b) S-dimethylaminopentyl a-cyclohexyl-fi-hydroxy-fiisopropyl-q-methylvalerate can be prepared by esterification of a-cyclohexyl-B-hydroxy-fi-isopropyl-y-methylvaleric acid with S-dimethylaminopentyl chloride according to the manipulative procedure given above in Example 1, part (b).

EXAMPLE 23 (a) a-Cyclohexyl 8 hydroxy 'y ethylcaproic acid (R=C H R'=H, R=CH(C H can be prepared by catalytic hydrogenation of a-phenyl-fl-hydroxy-y-ethylcaproic acid, M.P. 98-100 C. by the manipulative procedure described above in Example 1, part (a).

- (b) Hexamethyleniminoethyl a-cyclohexyl-fi-hydroxyyethylcaproate can be prepared by esterification of a-cyclohexyl-fl-hydroxy- -ethylcaproic acid with hexamethyleniminoethyl chloride according to the manipulative pro-- cedure given above in Example 1, part (b).

Example 24 (a) a-(4-Methylcyclo'hexyl)-fi-hydroxy-B-methylbutyric (R=4-CH3C5H10, R'=CH3, R=CH3) can be prepared by catalytic hydrogenation of a-p-tolyl) -}8-hydroxyfl-methylbutyric acid by the manipulative procedure above in Example 1, part (a).

(b) Z-diethylaminopropyl a-(4-methylcycl0hexyD-pmethylbutyrate can be prepared by esterification of a- (4-methyl-cyclohexyl-p-hydroxy-p-methylbutyric acid with r 1 3 2 diethylaminopropyl chloride. according tothe manipula; v p o e ur -gi en. above n xamp e pa (1 9-- I} claim:

1. A. comma d: e ected; f om the o p onsi in o mp u s hav n h o mu l /CCHCQ OYN=B Q 1: wherein R is a member of. the class consisting of the cyclohexyl group and lower-alkyl-substituted cyclohexyl groups, R is. a, member of; theclass. consisting of-hydro-. gen, lower-alkyl, -.8.-membered; cycloalkyl: and: lower-. alkylvsubstituted 5-8-membered; cycloalkyl groups, R" is a member of the group consisting of S-S-membered. cy-. oloalkyl, lower-alkyL-substitutediSe8vmemberedcycloalkyl, lower-alkyl, and lower-alkyl groups joined with R to. form, amember of? the class consisting of; 5:8-membered cycloalkyl groups and lower-a1kyl-substituted S-SH-mGmbered; cycloalkyl: groups, Y is a loweri-alkylene bridge. in which the free valences are on difierent; carbon atoms, and N=B, is a. member of theclass, consisting of dilower-alkylamino, polymethylenimino radicals. having from 5-, to 8-mcmber ed rings; and morpholinoradicals; and acid-addition and quaternary ammoniuru-v saltsthere- Of;

2. A, compound having the formula o-.- bH-cooY-N=B.. R OH wherein R is cyclohexyl, R and R" are lower-alkyl groups, Yi s a lower-alkylene bridge in which the free valences are on different carbon atoms, and N=B is a di-lower- 'alkvlamino radical.

3. A compound having the formula wherein R is cyclohexyl, R is hydrogen, R" is a loweralkyl group, Y is a lower-alkylene bridge in which the free valences are on difierent carbon atoms, and N=B is a di-lower-alkylamino radical.

4. A compound having the formula GH2*GE2 R C (JH-COO--YN=B wherein R is a cycloalkyl group, n is an integer from 1 to 4, Y is a lower-alkylene bridge in which the free valences are on different carbon atoms, and N=B is a dilower-alkylamino radical.

5. A compound having the formula wherein R is cyclohexyl, R and R" are lower-alkyl groups, Y is ethylene, and N=B is' a di-lower-alkylamino radical.

6. A compound having the formula wherein R is cyclohexyl, R is hydrogen, R" is a loweralkyl group, Y is ethylene, and N=B is a di-loweralkylamino radical.

7. A compound having the formula 14 wherein R is cyclohexyl, R and R" are lower-alkyl. groups, Y is ethylene, and -N=B is diethylamino.

8. A compound having the formula wherein R is cyclohexyl, R is hydrogen, R is a lowerl yl p. Y is e hy ene. nd N= s. ethy amin 9. A compound having the formula CH2CHQ R oqhn c 0 0-Y-N=B lva Cg! OH. wherein R is cyclohexyl, n is an integer from 1' to 4 Y is ethylene, and N=B, is a. di-loWer-alkylamino radical.

10. A compound having the formula CHz :CHg If,

G CH-CO OYN=B .2),fl? fi, whereinR; isicyelohexy-l, n is, aninteger from-1 to 4, Y is ethylene, and N=B is a diethylamino radical.

11. In the process for the preparation of a compound having the formula wherein. R is. a member of the class consisting of the cycloh exyl group and lower-alkyl-substituted cyclohexylgroups, R is amember of thelclass consisting of; hydrogen, loWer-alkyl, 5-8-mernbered cycloalkyl and loweralkyl substituted 5-8-membered-cyc1oalkyl' groups, R" is a member of the group consisting of 5-8-membered cycloalkyl, lower-alkyl-substituted 5-8 membered cycloalkyl, lower-alkyl, and lower-alkyl groups joined with R to form a member of the class consisting of 5-8-membered cycloalkyl groups and lower-alkyl-substituted 5-8-membered cycloalkyl groups, Y is a lower-alkylene bridge in which the free valences are on difierent carbon atoms, and N=B is a member of the class consisting of di-lower-alkylamino, polyrnethylenimino radicals having from 5- to S-membered rings and morpholino radicals, the steps which comprise selectively catalytically hydrogenating the aromatic ring of a compound having the formula wherein Ar is selected from the class consisting of phenyl and lower-alkyl-substituted phenyl groups, and heating between about 50 C. and C. the resulting acid having the formula 0- H-COOH R OH with a tertiary-aminoalkyl halide having the formula ZY-N=B wherein Z is halogen.

12. A compound having the formula C( JH-OOOH R" OH wherein R is a member of the class consisting of the cyclohexyl group and lower-alkyl-substituted cyclohexyl groups, R is a member of the class consisting of hydrogen, lower-alkyl, S-S-membered cycloalkyl and loweralkyl-substituted S-S-membered cycloalkyl groups, and R" is a member of the group consisting of 5-8-membered cycloalkyl, lower alkyl-substituted 5-8-membered cycloalkyl, lower-alkyl, and lower-alkyl groups joined with R to form a member of the class consisting of -8- membered cycloalkyl groups.

13. A compound having the formula wherein R is a member of the class consisting of the cyclohexyl group and lower-alkyl-substituted cyclohexyl groups, R is a member of the class consisting of hydrogen, lower-alkyl, 5-8-membered cycloalkyl and loweralkyl-substituted 5-8-membered cycloalkyl groups, and R" is a member of the group consisting of S-S-membercd cycloalkyl, lower-alkyl-substituted S-S-membered cycloalkyl, lower-alkyl, and lower-alkyl groups joined-with R to form a member of the class consisting of 5-8-membered cycloalkyl groups and lower-alkyl-substituted 5-8- membered cycloalkyl groups, which comprises selectively catalytically hydrogenating the aromatic ring of a compound having the formula wherein Ar is selected from the class consisting of phenyl and lower-alkyl-substituted phenyl groups.

17. B Diethylaminoethyl a cyclohexyl-B-hydroxy-flmethylvalerate.

18. fl-Diethylaminoethyl a-cyclohexyl-p-hydroxy-caproate.

19. B-Diethylaminoethyl cyclopentyl)acetate.

20. ,B-Diethylaminoethyl cyclohexyl) acetate.

21. fl-Diethylaminoethyl cycloheptyl) acetate.

22. a-Cyclohexyl-B-hydroxy-p-methylva1eric acid.

23. a-Cyclohexyl-B-hydroxycaproic acid.

24. a-Cyclohexyl-a-( l hydroxycyclopentyl) acetic acid.

25. a-Cyclohexyl-a-( l-hydroxycyclohenxyl)acetic acid.

26. a-Cyc1ohexy1-a-(l-hydroxycycloheptyl) acetic acid.

on cyclohexyl-m-( l-hydroxya cyc1ohexyl-a-( l-hydroxya cyclohexyl-a-( l-hydroxy References Cited in the file of this patent UNITED STATES PATENTS Miescher et a1. Dec. 9, 1941 Miescher et a1. Dec. 9, 1941 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS HAVING THE FORMULA
 12. A COMPOUND HAVING THE FORMULA
 16. THE PROCESS FOR THE PREPARATION OF A COMPOUND HAVING THE FORMULA 